Angiotensin II activates programmed myocyte cell death in vitro
Angiotensin II activates programmed myocyte cell death in vitro
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DOI：
10.1006/excr.1997.3477
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发表时间：
1997-03-15
影响因子：
3.7
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Cigola, E;Kajstura, J;Anversa, P
为探讨血管紧张素Ⅱ（angiotensin Ⅱ，Ang Ⅱ）是否能诱导新生大鼠心室肌细胞凋亡，用10（-9）M Ang Ⅱ体外处理心肌细胞24 h，用末端脱氧核苷酸转移酶（TUNEL）法和DNA凝胶电泳法检测Ang Ⅱ对心肌细胞程序性死亡的影响。血管紧张素II导致在形态学上的2.5倍增加的百分比与双链切割的DNA和生物化学的DNA片段的大小相等的单和寡核小体的形成的心肌细胞。此外，血管紧张素II刺激的特点是增加了37%的静息水平的细胞内钙和激活的钙依赖性内源性核酸内切酶。与此相反，pH依赖性内源性核酸内切酶并没有增强通过添加血管紧张素II。AT（1）受体拮抗剂氯沙坦可抑制Ang Ⅱ诱导的DNA损伤。类似地，钙螯合剂BAPTA-AM阻止了Ang II介导的细胞死亡。相反，钙离子载体A23187触发程序性细胞死亡。最后，选择性AT（2）受体亚型阻断剂PD 123319未能减少心肌细胞凋亡。总之，AT（1）受体的配体结合可能通过胞浆钙升高和钙依赖性内源性核酸内切酶的刺激启动程序性心肌细胞死亡。(C)北京：科学出版社.
To determine whether angiotensin II (Ang II) can induce apoptosis of neonatal ventricular myocytes, these cells were exposed to 10(-9) M Ang II for 24 h in vitro and the effects of this intervention on programmed myocyte cell death were examined by the terminal deoxynucleotidyl transferase assay and DNA gel electrophoresis. Ang II resulted morphologically in a 2.5-fold increase in the percentage of myocytes with double strand cleavage of the DNA and biochemically in the formation of DNA fragments equal in size to mono- and oligonucleosomes. Moreover, Ang II stimulation was characterized by a 37% increase in resting level of intracellular calcium and the activation of calcium-dependent endogenous endonuclease. In contrast, pH-dependent endogenous endonuclease was not enhanced by the addition of Ang II. Ang II-induced DNA damage was inhibited by the AT(1) receptor antagonist, losartan. Similarly, the calcium chelator, BAPTA-AM, prevented Ang II-mediated cell death. Conversely, the calcium ionophore, A23187, triggered programmed cell death. Finally, the selective AT(2) receptor subtype blocker, PD123319, failed to reduce myocyte apoptosis. In conclusion, ligand binding of AT(1) receptors may initiate programmed myocyte cell death via an elevation in cytosolic calcium and the stimulation of calcium-dependent endogenous endonuclease. (C) 1997 Academic Press.